Table 2.

Studies Analyzing Association of Blood Cryptococcal Antigen Titer and Subsequent Cryptococcal Meningitis and/or Death

Country	Year	Study design	Association between blood CrAg titer and CM and/or mortality	Notes	Ref
Association between blood CrAg titer and subsequent CM and/or mortality
South Africa	2009	Retrospective analysis of CrAg titers (using Latex Agglutination, LA) on pre-ART blood samples from 46 patients.	Higher baseline titer associated with increased risk of mortality (p=0.02), subsequent cryptococcal meningitis (p=0.03) and relapse (all >512) within 1 y.	No baseline LP performed. Symptoms and fluconazole use unknown.	[1]
Tanzania	2011	CrAg screening of all HIV positive hospital admissions. Serum CrAg titers (LFA) on 17/333 CrAg-positive patients.	Higher titer associated with mortality (p=0.004).	All symptomatic, 15/17 had cryptococcal meningitis.	[17]
Tanzania	2015	Retrospective analysis of blood CrAg titers (using LFA) on pre-ART blood samples from 21 asymptomatic patients.	Titer of >160 associated with subsequent cryptococcal meningitis (adjusted OR, 4.83; 95% CI, 1.24–8.41; P = .008) within 1 y.	3 patients with titers ≤160 died of unknown causes.	[11]
Uganda	2016	Cluster randomized trial of CrAg screen and treat strategy. CrAg titers (LFA) on 151 asymptomatic patients.	Titer of ≥160 associated with subsequent cryptococcal meningitis (HR 9.2, 95% CI 2.14-39.58, p<0.01) (unpublished data)	Increased risk of death or subsequent cryptococcal meningitis if titer ≥160 and CD4 ≤50.	[20]

Abbreviations: ART, antiretroviral therapy; CI, confidence interval; CM, cryptococcal meningitis; CrAg, cryptococcal antigen; HIV, human immunodeficiency virus; HR, hazard ratio; LA, latex agglutination; LFA, lateral flow assay; LP, lumbar puncture; OR, odds ratio.